Mechanism study on the attenuation of cerebral ischemia-reperfusion injury by LBP extract through regulation of SIRT1/PGC-1α axis.

Abstract

Objective: This study aims to determine if Lycium barbarum polysaccharides (LBP) extract attenuate oxidative stress by regulating the SIRT1/PGC-1α axis, potentially ameliorating oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage.

Methods: A cellular hypoxia/reoxygenation model (OGD/R) using HT22 cells was established to simulate cerebral ischemia-reperfusion injury. Cells were allocated into four groups: normal (Control), hypoxia (OGD/R), LBP extract-treated (OGD/R + LBP at 25, 50, 100 μg/mL), and SIRT1-inhibited (OGD/R + S100). Western blot and qPCR were performed to detect the expression of pathway-related factors, oxidative stress, mitochondrial function, and apoptosis-related factors.

Results: Compared to the Control group, the OGD/R group exhibited significantly reduced cell survival, increased LDH release, apoptosis rate, and reactive oxygen species (ROS) levels. After intervention with LBP extract, cell survival increased, LDH release, ROS levels, and apoptosis rates reduced. The above injuries were associated with the inhibition of the SIRT1/PGC-1α pathway. LBP extract can attenuate the hypoxia-reperfusion-induced inhibition of the SIRT1/PGC-1α pathway and reverse the resulting high levels of oxidative stress and apoptosis, ultimately ameliorating cellular injury.

Conclusion: LBP extract's protective effects against ischemia-reperfusion injury in HT22 cells appear linked to the modulation of the SIRT1/PGC-1α pathway and a reduction in oxidative stress.